1. Field of the Invention
This invention relates to an synergistic antibacterial combination of a noncationic halogenated hydroxydiphenyl ether and a hydrogenated lupulone derived from beer hops and more particularly to an oral composition containing such combination which exhibits substantially increased antibacterial efficacy against plaque causing oral bacteria.
2. The Prior Art
It is difficult to predict the efficacy of antibacterial agents when incorporated in any delivery vehicle and particularly in oral compositions. For example, dental plaque is a soft deposit which forms on teeth as opposed to calculus which is a hard calcified deposit on teeth. Unlike calculus, plaque may form on any part of the tooth surface, particularly at the gingival margin and is implicated in the occurrence of gingivitis. Cationic antibacterial compounds such as chlorhexidine, benzthonium chloride and cetyl pyridinium chloride have been used by the art as antibacterial antiplaque agents in oral compositions. However, such agents are generally not effective when there is also present in the oral composition an anionic surfactant required for the effective performance of oral compositions such as toothpaste and mouthrinses.
Noncationic antibacterial materials are compatible with anionic surfactants in oral compositions and noncationic halogenated hydroxydiphenyl ethers such as Triclosan have been effectively employed in commercial oral compositions as antibacterial antiplaque agents when mixed with neutral ingredients such as humectants, abrasives and thickeners conventionally used in the formulation of oral compositions. Notwithstanding the antibacterial efficacy of Triclosan, there is a continuing interest in the oral composition field for antibacterial agents which are compatible with anionic surfactants and which improve the efficacy of noncationic halogenated hydroxydiphenyl ethers such as Triclosan.
In addition to Triclosan, beta-acids, also known as lupulones, derived from beer hops, are known to the art to exhibit antibacterial action in oral compositions. For example, U.S. Pat. No. 3,932,603 discloses that hop extract resins, such as lupulone and humulone, are effective as antimicrobials against cariogenic streptococci. U.S. Pat. No. 5,370,863 discloses oral compositions containing hop acids which inhibit gram positive bacteria and plaque formation and periodontal disease.
The beta-acids are also known to inhibit the growth of food pathogens, such as Listeria monocytogenes (U.S. Pat. Nos. 5,286,506; 5,455,038). In addition the hydrogenated form, hexahydrolupulone inhibits the growth of certain Lactobacilli (U.S. Pat. No. 5,082,975). Hydrogenated lupulones appear to be more active and stable than their non-hydrogenated parent compounds. For example, hexahydrocolupulone is believed to be more antibacterial active than colupulone while hexahydrolupulone has been found to be more stable than lupulone. Hexahydrocolupulone can be made by the chemical hydrogenation of colupulone using a number of methods known in the art. For example, hydrogenation can be achieved with platinum (IV) oxide as a catalyst as described by Riedl (Ber. 89:1863 (1956) or by Carson (J. Am. Chem. Soc. 73:1850 (1951). A method for preparing hexahydrolupulone is described in U.S. Pat. No. 5,082,975.